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Cilostazol versus aspirin for secondary prevention of vascular events after a stroke of arterial origin

Stroke is a public health problem. As lower and middle income countries make rapid economic progress they face the additional health burden of diseases of affluence like stroke and heart attacks. Unlike heart attack, stroke is a disease caused by more than one mechanism. In Asians, a larger proportion of ischaemic stroke is due to narrowing of the arteries at the base of the brain. Compared to Caucasians, Asians are more likely to have bleeds into their brain matter causing stroke, because of uncontrolled high blood pressure. The medication cilostazol thins the blood by blocking platelet accumulation and appears, from early reports, to be more effective than aspirin in the prevention of stroke, heart attacks and death from vascular causes in patients with stroke. This may be due to its inherent effectiveness, as well as chances of fewer brain bleeds. In this review of two randomised trials involving 3477 participants, we found that cilostazol was more effective for the prevention of stroke, heart attack and death from vascular causes in Asian patients with stroke. In terms of safety, it causes more side effects than aspirin but less serious bleeding in the brain and the body.

Authors' conclusions:

Cilostazol is more effective than aspirin in the prevention of vascular events secondary to stroke. Cilostazol has more minor adverse effects, although there is evidence of fewer bleeds.

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Background:

Aspirin is widely used for secondary prevention after stroke. Cilostazol has shown promise as an alternative to aspirin in Asian people with stroke.

Objectives:

To determine the relative effectiveness and safety of cilostazol compared directly with aspirin in the prevention of stroke and other serious vascular events in patients at high vascularrisk for subsequent stroke, those with previous transient ischaemic attack (TIA) or ischaemic stroke of arterial origin.

Search strategy:

We searched the Cochrane Stroke Group Trials Register (last searched September 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to May 2010) and EMBASE (1980 to May 2010). In an effort to identify further published, ongoing and unpublished studies we searched journals, conference proceedings and ongoing trial registers, scanned reference lists from relevant studies and contacted trialists and Otsuka Pharmaceutical Co Ltd.

Selection criteria:

We selected all randomised controlled trials (RCTs) comparing cilostazol with aspirin where participants were treated for at least one month and followed systematically for development of vascular events.

Data collection and analysis:

Data extracted from eligible studies included: (1) a composite outcome of vascular events (stroke, myocardial infarction or vascular death) during follow up (primary outcome); (2) separate outcomes of stroke (ischaemic or haemorrhagic, fatal or non-fatal), myocardial infarction (MI) (fatal or non-fatal), vascular death and death from all causes; and (3) main outcomes of safety including any intracranial, extracranial or gastrointestinal (GI) haemorrhage and other outcomes during treatment follow up (secondary outcomes). We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all included studies.